title: An IL-12 DNA vaccine co-expressing Yersinia pestis antigens protects against pneumonic plague.
abstract: Pneumonic plague remains problematic in endemic areas, and because it can be readily transmitted and has high mortality, the development of efficacious vaccines is warranted. To test whether stimulation of cell-mediated immunity with IL-12 will improve protective immunity against plague, we constructed two IL-12 DNA vaccines using a bicistronic plasmid encoding the protective plague epitopes, capsular (F1) antigen and virulence antigen (V-Ag) as F1-V fusion protein and V-Ag only, respectively. When applied intramuscularly, antibody responses to F1- and V-Ag were detectable beginning at week 6 after 3 weekly doses, and F1-Ag protein boosts were required to induce elevated Ab responses. These Ab responses were supported by mixed Th cell responses, and the IL-12/V-Ag DNA vaccine showed greater cell-mediated immune bias than IL-12/F1-V DNA vaccine. Following pneumonic challenge, both IL-12 DNA vaccines showed similar efficacy despite differences in Th cells simulated. These results show that IL-12 can be used as a molecular adjuvant to enhance protective immunity against pneumonic plague.
authors.affiliation: Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717-3610, USA.
authors.forename: Hitoki
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Teri
authors.initials: T
authors.lastname: Hoyt
authors.forename: Richard
authors.initials: R
authors.lastname: Bowen
authors.forename: Xinghong
authors.initials: X
authors.lastname: Yang
authors.forename: Kathryn
authors.initials: K
authors.lastname: Crist
authors.forename: Sarah
authors.initials: S
authors.lastname: Golden
authors.forename: Massimo
authors.initials: M
authors.lastname: Maddaloni
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D005260:Female; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010930:Plague / Q000276:immunology / Q000517:prevention & control*; D010931:Plague Vaccine / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D013154:Spleen / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D010931:Plague Vaccine; D019444:Vaccines, DNA; D018664:Interleukin-12